Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Levetiracetam, Lacosamide and Ketamine as Adjunctive Treatment of Refractory Status Epilepticus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02726867
Recruitment Status : Withdrawn (No participants enrolled)
First Posted : April 4, 2016
Last Update Posted : August 29, 2017
Sponsor:
Information provided by (Responsible Party):
Pavel Klein, Mid-Atlantic Epilepsy and Sleep Center, LLC

Tracking Information
First Submitted Date  ICMJE December 12, 2014
First Posted Date  ICMJE April 4, 2016
Last Update Posted Date August 29, 2017
Study Start Date  ICMJE February 2014
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2016)
Cessation of status epilepticus by EEG. [ Time Frame: 60 minutes ]
The cessation of ictal epileptic EEG activity measured by EEG.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2016)
Cessation of status epilepticus by clinical examination [ Time Frame: 60 minutes ]
Measurement of the time to status epilepticus cessation by clinical examination.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: April 1, 2016)
  • Recurrence of status epilepticus. [ Time Frame: 72 hours ]
    The recurrence of status epilepticus in responders in during the 72 hours of monitoring.
  • Rate of early treatment discontinuation [ Time Frame: 72 hours ]
    Rate of treatment discontinuation within 72 hours.
  • Duration of hospitalization [ Time Frame: 3 months ]
    Investigators will count the number days of hospitalization.
  • Number of participants with neurological deficit. [ Time Frame: 3 months ]
    Investigators will identify the number of patients with neurological deficit at 3 months are the other measure outcomes.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Levetiracetam, Lacosamide and Ketamine as Adjunctive Treatment of Refractory Status Epilepticus
Official Title  ICMJE Evaluation of Efficacy and Safety of Levetiracetam, Lacosamide and Ketamine as Adjunctive Treatment of Refractory Status Epilepticus
Brief Summary The purpose of the study is to evaluate the efficacy and safety of levetiracetam , lacosamide and ketamine treatment of refractory status epilepticus. This will be a randomized, open-label, four-arm pilot study comparing time to cessation of refractory status epilepticus, determined by continuous EEG monitoring, in patients with refractory status epilepticus. Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical status epilepticus for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) either 4000 mg levetiracetam, 600 mg lacosamide (Group B), 2.5 mg/kg ketamine or phenobarbital 15 mg/kg phenobarbital (Group D)
Detailed Description

40 18-70 year old men and women with refractory status epilepticus, defined as status epilepticus continuing for >1 hour after completion of standard treatment with lorazepam (or midazolam) and i.v. phenytoin (or fos-phenytoin),will be enrolled. Participants will be randomized into four treatment arms, levetiracetam 4000 (Group A, n=10), lacosamide 600 mg (Group B, n=10), ketamine 2.5 mg/kg (group C,n=10),and phenobarbital 15 mg/kg (Group D, n=10) in a 1:1:1:1 ratio. Baseline evaluations will include continuous EEG, phenytoin levels prior to study intervention, CBC, CMP, serum Ca, Po4 and Mg.

Treatment will consist of levetiracetam 4000 mg i.v. over 10 minutes, lacosamide 600 mg i.v. over 10 minutes, ketamine 2.5 mg/kg over 10 minutes, or phenobarbital 15 mg/kg mg i.v. at 100 mg/minute rate.

Participants will be evaluated with ongoing physical examination and continuous EEG monitoring. Continuous EEG monitoring will be started before initiation of the study treatment, with documentation of electrographic status epilepticus. It will continue throughout the treatment period. Subjects will be observed for 1 hour clinically and with continuous EEG monitoring for cessation of SE. Participants in whom status epilepticus stops within 60 minutes of completion of study treatment will continue to receive phenytoin (150 mg i.v. q 12 hours, standard dose) and the study medication (levetiracetam 1500 mg i.v. q 12 hourly, lacosamide 300 mg q 12 hourly, ketamine 50 mg qid (vs. 40 mcg/kg/min i.v. infusion, as clinically applicable, or phenobarbital 90 mg i.v. q 12 hourly). Continuous EEG monitoring will continue for 72 hours to monitor for relapse of status epilepticus. Participants in whom status epilepticus fails to stop within 60 minutes after completion of study treatment ("non-responders") will undergo standard treatment with medically-induced coma, with intubation/ventilation and i.v. midazolam or propofol treatment at a dose to be titrated to EEG effect of "burst suppression" or suppression of all background activity. All patients, responders and non-responders alike, will continue treatment with phenytoin i.v., 150 mg q 12 hourly or, for conscious patients, 300 mg p.o. qhs for 72 hours after completion of study treatment. In patients requiring medical coma after study treatments (non-responders), medical coma will be discontinued after 48 hours. All participants will continue to be monitored with continuous EEG for 72 hours from completion of study treatment. If status epilepticus returns during this time, medical coma will be re-instituted and patients will be treated according to standard clinical care for prolonged SE

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Epilepsy
  • Status Epilepticus
Intervention  ICMJE
  • Drug: levetiracetam
    Treatment will consist of LEV 4000 mg i.v. over 10 minutes.
    Other Name: Keppra
  • Drug: lacosamide
    Treatment will consist of LCM 600 mg i.v. over 10 minutes
    Other Name: Vimpat
  • Drug: Ketamine
    Treatment will consist of KET 2.5 mg/kg over 10 minutes
    Other Name: Ketalar
  • Drug: Phenobarbital
    Treatment will consist of PHB 15 mg/kg mg i.v. at 100 mg/minute rate
    Other Name: Phenobarb
Study Arms  ICMJE
  • Active Comparator: levetiracetam
    Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) 4000 mg levetiracetam.
    Intervention: Drug: levetiracetam
  • Active Comparator: lacosamide
    Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) 600 mg lacosamide.
    Intervention: Drug: lacosamide
  • Active Comparator: ketamine
    Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) 2.5 mg/kg ketamine.
    Intervention: Drug: Ketamine
  • Active Comparator: phenobarbital
    Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin (PHT) with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after PHT loading will receive intravenously (i.v.) phenobarbital 15 mg/kg.
    Intervention: Drug: Phenobarbital
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 28, 2017)
0
Original Estimated Enrollment  ICMJE
 (submitted: April 1, 2016)
40
Actual Study Completion Date  ICMJE November 2016
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age 18-70
  2. Ability and willingness by surrogates to signed informed consent form.
  3. Clinically and electrographically documented ongoing SE lasting ≥1 hour- ≤24 hours

Exclusion Criteria:

  1. Creatinine > 2.5 mg/dl
  2. Any systemic illness or unstable medical condition that might pose additional risk, including: cardiac, metabolic or endocrine disturbances, renal or liver disease
  3. Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements
  4. Pregnancy
  5. Inability or unwillingness of subject or legal surrogate to give written informed consent
  6. Known allergy to a study drug
  7. Hypo- or hyperglycemia as cause of SE
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02726867
Other Study ID Numbers  ICMJE MAES-003
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Pavel Klein, Mid-Atlantic Epilepsy and Sleep Center, LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Mid-Atlantic Epilepsy and Sleep Center, LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pavel Klein, M.D. Mid-Atlantic Epilepsy and Sleep Center
PRS Account Mid-Atlantic Epilepsy and Sleep Center, LLC
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP